A pilot study of childhood leukemia patients living near Colorado’s oil and gas drilling sites recently led to an American Cancer Society (ACS) grant award for CU Cancer Center member Lisa McKenzie PhD, MPH.
Research and treatment of head and neck cancers at the University of Colorado Cancer Center reached a new level this month with a highly competitive Specialized Programs of Research Excellence (SPORE) grant from the National Cancer Institute (NCI). The SPORE was approved by NCI Scientific Program leadership for FY2021 funding; the projected starting date is July 1.
By now, we’ve all heard about the importance of cancer screening. But for those with a detected cancer, a new article highlights that the removal of the malignancy might not be where you should stop in your health journey.
While many cancer types have added new treatments including genetically targeted drugs and immunotherapies, treatment for the rare types of cancer known as sarcomas have remained largely the same for about two decades. Now, two grants to University of Colorado Cancer Center researchers from the Sarcoma Foundation of America hope to change this.
The University of Colorado Cancer Center is excited to announce that the “interim” title before Christopher Lieu, MD, has been removed making him the Associate Director of Clinical Research. Dr. Lieu was in the interim role for 8 months before being named the associate director. Dr. Lieu, who is also the director of the gastrointestinal medical oncology program, joined the CU School of Medicine faculty in 2011. For the past nine years Dr. Lieu has been an investigator on numerous CU Cancer Center studies, including taking the lead on early-onset colorectal cancer research. Dr. Lieu received the National Cancer Institute Cancer Clinical Investigator Team Leadership Award in 2017. Additionally, Dr. Lieu is the Vice-Chair of the National Cancer Institute Colon Cancer Task Force and on the National Comprehensive Cancer Network Panel for Neuroendocrine Cancers.
Radiation is one of our best weapons against cancer. However, after radiation treatments, cancer often returns. Now an 2-year, $2 million National Cancer Institute (NCI) award to Boulder-based startup SuviCa, Inc. co-founded by CU Boulder and CU Cancer Center investigator, Tin Tin Su, PhD, hopes to find drugs that augment the effect of radiation to keep cancer at bay.
The difference in cancer outcomes between urban and rural Americans is so pronounced that the National Institutes of Health list “rurality” as a risk factor for death from the disease. For example, the 5-year survival rate for Coloradoans diagnosed with lung cancer is 70 percent, but the 5-year survival forruralColoradoans with the same diagnosis is only 55 percent. While we certainly continue to learn more about this urban-rural cancer care gap, the picture is already pretty clear: Not just in Colorado, but across the country, rural Americans diagnosed with cancer are more likely to die from their conditions than are urban Americans. The question has been what to do about it.
University of Colorado Cancer Center member, Tejas Patil, MD, received the John Fisher Legacy Fellowship Award at the International Association for the Study of Lung Cancer (IASLC) World Conference held in Barcelona last month. Patil is the first physician worldwide to receive the prestigious $50,000 grant, which Patil will use to further his research in detecting lung cancer recurrence in early stages.
One of the International Atomic Energy Agency’s (IAEA) missions, in addition to being the world’s central organization for the peaceful use of nuclear technology, is to promote the safe, high quality use of radiation in medicine. Recently, the IAEA hosted a competition that encouraged medical professionals to contribute their good ideas for radiation safety, particularly how to cultivate a strong culture of safety. Guess what? Researchers from University of Colorado Cancer Center Department of Radiation Oncology working at UCHealth University of Colorado Hospital won! Their innovation? Recognizing that safety can be fun.
The National Cancer Institute (NCI) is set up to fund individual projects in fields like genomics, computational biology, and pathology. Now researchers at University of Colorado Cancer Center are taking advantage of an innovative new program in cancer systems biology to combine the three research areas, earning a prestigious “U01” grant to study the complex genetic drivers of aggressive prostate cancer. By combining the tools of pathology, computational modeling and genomics, the project hopes to discover and test therapeutic interventions for three molecularly distinct types of prostate cancer.
“Prostate cancer is defined by its pathology – you take a biopsy, give it to a pathologist, and they score it, for example they will characterize it as ‘pathological stage 3 disease.’ What we want to do is to understand how genetics contributes to driving aggressive pathology. By understanding what pathways and processes are dysregulated by distinct genetic alterations, we can start to explore therapeutic options to match the genetic alterations,” says James Costello, PhD, CU Cancer Center investigator and assistant professor in the Department of Pharmacology at the CU School of Medicine.
In cancers like melanoma, there tends to be a single genetic driver.
“You have mutations in oncogenes such as BRAF or RAS that drives disease,” says Scott Cramer, PhD, investigator at the CU Cancer Center and professor in the CU School of Medicine Department of Pharmacology. “But in prostate, it’s tricky. Prostate cancer tends to be driven by the loss of tumor-suppressor genes – for example, you lose TP53 and the tumor can grow. In prostate, we find that aggressive disease is often associated with loss of multiple tumor suppressors.”
The field of cancer research is getting better and better at turningoffoncogenes that cause cancer. However, the field is far less adept at therapeutically targeting cancers where good genes are lost.This means that in prostate cancer and other cancers created bylossof tumor suppressors, treatment isn’t as simple as switching these lost genes back on. Instead, this project hopes to discover what else happens in prostate cancers with loss of these tumor suppressor genes – possibly, in this tangled network of cause-and-effect, turningoffa tumor suppressor like TP53 may turnonanother gene that aids cancer growth. And if that’s the case, Costello, Cramer, and colleagues would have a target they could do something about – a target gene they could turn off.
Likewise, “In prostate, you get big deletions in chromosomes – there are multiple genes in there and we need to know which ones are the causal drivers of aggressive disease,” Cramer says.
In other words, deleted along with these known tumor-suppressor genes like TP53, may be the loss of many other genes. Some of these losses are unimportant – only about 1.2 percent of our genome is actually manufactured into proteins. But some losses may be additional drivers of cancer.
To discover these genetic drivers of prostate cancer, Costello and Cramer will turn off various combinations of genes in mouse models of the disease to see which combinations grow into aggressive cancers. Then the team will look inside these models of aggressive cancer to see which genetic pathways are affected.
“We end up with the genetically altered cells that drive the disease, which allows us to ask what is the most likely therapeutic target? Then we can treat mouse models with drugs and see if it’s successful,” Costello says. If these studies are promising the next step may be clinical trials in men with this aggressive form of prostate cancer.
Until recently, the project would have struggled to find funding.
“When you submit a grant, it gets evaluated by a ‘study section,’” says Cramer. “Most study sections are very focused – you submit this project to a pathology study section and they might not get the computational modeling that is used to help make sense of genome-wide measurements to identify therapeutic targets. But if you submit the grant to a computational modeling study section, they don’t get the pathology side and tend to score it poorly. The balance is tricky.”
With only 8 percent of cancer research project grant applications earning funding, even perceived weakness or misinterpretations by a reviewer in the study section can be fatal.
“The National Institutes of Health recognized there were research areas they wanted to fund that weren’t getting funded in standard study sections, so they developed the Cancer Systems Biology Consortium, for which the U01 is one mechanism to foster collaborations like this,” Costello says.
Despite decades of effort, no one set of tools has been able to point to the genes driving prostate cancer. Now with three sets of tools – genomics, computational modeling, and pathology – Cramer, Costello and CU Cancer Center colleagues hope to finally pinpoint the causes of aggressive prostate cancers. Knowing the cause is an important step toward finding a cure.
Patients aren’t the only ones affected by cancer. Often alongside patients are family caregivers who struggle to keep their own lives on track while supporting their loved one’s treatment and recovery. It’s not easy. For example, a studyshowed that stress increases a family caregiver’s chance of death by 63 percent over four years. Now a nearly $4M grant from the National Cancer Institute to researchers at University of Colorado Cancer Center seeks to lessen the impacts of stress specifically on cancer caregivers who are also employed. The project hopes to help caregivers manage the demands of their jobs and their lives, while also meeting the day-to-day needs of their loved one with cancer.
Clinical trials bring new treatments to Colorado patients, often offering innovative options years before they are available to patients outside academic medicine. The problem is that even after laboratory work and animal studies show the promise of a new cancer treatment, opening and enrolling a human clinical trial requires a painstaking process of planning and approvals. The faster doctors and administrators can accomplish this work, the sooner a clinical trial becomes available. Now a new grant from the National Cancer Institute will help University of Colorado Cancer Center speed this process of clinical trial approval, making more trials available sooner to patients who need them.
“Trials are the lifeblood of the Cancer Center – it’s how we move cancer treatments forward. This grant will help to ensure we’re on the cutting edge of new therapies. The earlier we can get a trial open, the earlier we can start offering it to patients,” says Victor Villalobos, MD, PhD, medical director of the CU Cancer Center Cancer Clinical Trials Office.
The competitive, two-year grant, called a Cancer Clinical Investigator Team Leadership Award (CCITLA), will allow Villalobos to, in his words, “buy some time back from the clinic to focus on being medical director.” His goals include reorganizing the Cancer Clinical Trials Office to improve trials’ time-to-open, a metric that can also entice drug companies to offer new treatments in Colorado.
Between the discovery of a new treatment and its delivery to patients is the often overlooked and incredibly complex process of clinical trial design and approval. And while clinical trial administration may not grab headlines like the discovery of a new way to fight cancer or the first patient who benefits from treatment, the process of deciding exactly how, when and to whom a trial is offered is an essential step toward the ability to more successfully fight the disease. Simply, this CCITLA will allow Villalobos and his team to help Coloradoans fight cancer better.
Jean Mulcahy-Levy, MD, has spent a decade researching how, why and when cells eat themselves. Healthy cells use this process, called autophagy, to recycle unneeded bits of themselves, often to survive periods of stress. Unfortunately, cancer cells use autophagy as well and for similar reasons – autophagy can help cancer cells survive the stress of drugs designed to kill them.
In this episode of "How This Is Building Me," Drs Camidge and Vokes discuss the span of countries and institutions along Dr Vokes’ journey to MD Anderson Cancer Center, how Dr Vokes balances research and work in the clinic, and how the correct mentors can help shape career paths in oncology.